CRC 858 B05 - Functional Regulation of ABC Transporters of the Multi-Drug-Resistance by Cooperative Interactions

Basic data for this project

Description

The main target of project B5 is to get a deeper insight into the cooperative interaction of both subunits in ABC transporters (ABC = ATP binding cassette) that is influenced by the transported substrates and by hydrolysis of ATP. These efflux proteins, fundamental e.g. for the Multi-Drug-Resistance, consist of two - often covalently bond - heterological or homological protein subunits. Both subunits contain a ATP binding site. The various compounds transported are e.g. drugs, cholesterol, bile salts, lipids and even complete proteins. The mechanism of this transport is not understood to date. We take into account a cooperative interaction between these substrates and the protein subunits, modulating the biological activity. A change in the conformation may induce ATP hydrolysis and start the active transport process. It is assumed, that ATP functions not only as a source of energy, but also regulates the efficiency of the transport. We try to analyze the ATP hydrolysis process and the transport activity with the help of reconstituted vesicle systems in suspension, with surface attached proteoliposomes and with solid state supported membranes.